ID | 65718 |
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Kemmotsu, Naoya
Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Zhu, Li
Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nagasaki, Joji
Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Otani, Yoshihiro
Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ueda, Youki
Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Dansako, Hiromichi
Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Fang, Yue
Department of Microbial and Biochemical Pharmacy, School of Pharmacy, China Medical University
Date, Isao
Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Togashi, Yosuke
Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Abstract | Hydrogen peroxide (H2O2) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H2O2 and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H2O2 on antitumor immunity remain unclear. To investigate the effects of H2O2, especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H2O2 mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H2O2/RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H2O2 or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor-draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H2O2/RT combination group. In addition, analyses of tumor-infiltrating lymphocytes showed that the number of CD8+ (cluster of differentiation 8) T cells and the frequency of IFN-γ+ (interferon gamma) CD8+ T cells were higher in the noninjected/nonirradiated tumors in the H2O2/RT group compared to those in the other groups. PD-1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H2O2/RT group. Intratumoral injection of H2O2 combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD-1 blockade. These findings promote the development of H2O2/RT therapy combined with cancer immunotherapies, even for advanced cancers.
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Keywords | abscopal effect
dendritic cell
hydrogen peroxide
radiosensitizer
radiotherapy
tumor-draining lymph node
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Published Date | 2023-07-23
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Publication Title |
Cancer Science
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Volume | volume114
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Issue | issue10
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Publisher | Wiley
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Start Page | 3848
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End Page | 3856
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ISSN | 1347-9032
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2023 The Authors.
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File Version | publisher
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Related Url | isVersionOf https://doi.org/10.1111/cas.15911
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License | https://creativecommons.org/licenses/by-nc/4.0/
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Citation | Kemmotsu, N, Zhu, L, Nagasaki, J, et al. Combination therapy with hydrogen peroxide and irradiation promotes an abscopal effect in mouse models. Cancer Sci. 2023; 114: 3848-3856. doi:10.1111/cas.15911
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